The Cinderella tree, Quillaja saponaria – A soap story

Abstract

Our current understanding of plants has been shaped by the entwining of different cultures. The Chilean soapbark tree, traditionally valued as a source of natural soap, was shown by serendipitous research in France in the 1900s to produce compounds that can boost the immune response to vaccines. One of these compounds, QS-21, was approved for use in human vaccines in 2017 and is now valued at >$100,000/g because of its growing importance as a vaccine adjuvant. This review tells the story of the humble soapbark tree and its elevation to fame as the source of one of the most sought-after naturally made immunostimulants. Summary: The Chilean soapbark tree, Quillaja saponaria Molina, grows in the central part of Chile. As its name suggests, the tree is a natural source of soap. Indeed, the name Quillaja is derived from the indigenous Chilean word ‘küllay’, which means ‘soap’. Soapbark is not the only plant to produce natural soaps. Other examples include the perennial soapwort (Saponaria officinalis), which grows in Europe and has historically been used as a source of gentle soap for washing delicate fabrics, including allegedly the Turin shroud; and Sapindus mukorossi (soapberry or soapnut), which grows in temperate and tropical regions of the world. The soapy properties of these plants are due to their production of glycosylated compounds known as saponins. In fact, saponins are found across the Plant Kingdom, not just in species with ‘soap’ in their names, and are one of the largest groups of plant natural products. The major saponin produced by Q. saponaria, which is known as QS-21, is a potent immunostimulant and has been approved for use in human vaccines. QS-21, which is the first naturally occurring plant glycoside to be used as an adjuvant, is a highly complex molecule that is produced only by Quillaja. This review covers the history of the soapbark tree, the discovery of QS-21 and the potential for making the next generation of saponin vaccine adjuvants using engineering biology approaches.